The immune system is the defense system of the organism against disease, through its ability to detect a wide variety of infectious agents, such as viruses and bacteria, and other parasitic agents, such as parasitic worms, by distinguishing these agents from the organism's own healthy tissue. Another important role of the immune system is to identify and eliminate tumors. Tumor growth and survival in an organism can be in a large part attributed to a number of mechanisms acquired by tumor cells to evade the immune system.
In the treatment or prevention of certain disease states, it may be beneficial to modulate the activity of the immune system, i.e. to induce, enhance, or suppress the immune response. For example, in the treatment of certain cancers, it may be desirable to provide treatments that activate and/or allow immune cells to recognize, attack, and destroy tumor cells that have developed immune evasion mechanisms. Activation of the immune system may also be part of a vaccination strategy against an infectious agent or a tumor. In other instances, it may be beneficial to downregulate or suppress the immune response to allow for greater immune tolerance. This is the case in the prevention and treatment of autoimmune diseases, which result from a hyperactive immune system that attacks normal tissues as if they were foreign organisms. Immune suppression is also a desirable treatment method in the prevention of organ transplant rejection.
The current invention relates to the polynucleotides encoding polypeptides of interest which may modulate the immune response. The polypeptides of interest may be expressed on the surface of immune cells or tumor cells, enabling the recognition of the tumor cells by the immune system and countering tumor immune evasion. In some aspects, the polypeptides of interest may comprise secreted proteins, such as cytokines and growth factors, which may stimulate immune cells to proliferate, differentiate and attack tumor cells, or alternatively function in a suppressive capacity, for example to inhibit the adaptive immune response in the treatment of autoimmune diseases.
The present invention addresses the need to selectively modulate the immune response by providing polynucleotides encoding polypeptides of interest which may have structural and/or chemical features that avoid one or more of the problems of nucleic acid based therapies known in the art, for example, features which are useful for optimizing formulation and delivery of nucleic acid-based therapeutics while retaining structural and functional integrity, overcoming the threshold of expression, improving expression rates, half-life and/or protein concentrations, optimizing protein localization, and avoiding deleterious bio-responses such as the immune response and/or degradation pathways. These barriers may be reduced or eliminated using the present invention.